title: CYP2W1 polymorphism: functional aspects and relation to risk for colorectal cancer.
abstract: OBJECTIVE
  This study aims to investigate the possible association between the risk of colorectal cancer (CRC) and allelic variants of CYP2W1 and their functional properties.
  
  
  METHODS
  The distribution of three different CYP2W1 alleles (CYP2W1*1, CYP2W1*2 and CYP2W1*6) in 1785 CRC patients and 1761 healthy blood donors was determined using the TaqMan(®) (Applied Biosystems, CA, USA) allelic discrimination assay or allele-specific amplification. Corresponding gene products (CYP2W1.1, CYP2W1.2 and CYP2W1.6) were expressed in human colon cancer SW480 cells and their activities towards two different substrates, the duocarmycin analogs ICT2706 and ICT2726, were monitored.
  
  
  RESULTS
  No significant differences in the distribution of CYP2W1*1, CYP2W1*2 and CYP2W1*6 alleles were found between CRC patients and controls. The CYP2W1.1, CYP2W1.2 and CYP2W1.6 variant enzymes were expressed at the similar levels in the transfected SW480 cells and had comparable kinetics in terms of the metabolism of the duocarmycin ICT2726, as well as in the bioactivation of ICT2706 into a cytotoxic product.
  
  
  CONCLUSIONS
  These epidemiological data obtained from a large population of CRC patients and controls cannot confirm the previously suggested decreased risk for CRC among carriers of CYP2W1*2. On the molecular level, this conclusion is further supported by the similar catalytic characteristics of the CYP2W1.1, CYP2W1.2 and CYP2W1.6 variants of CYP2W1.
authors.affiliation: Department of Molecular Medicine & Surgery, Karolinska Institutet & Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Stenstedt
authors.forename: Sandra
authors.initials: S
authors.lastname: Travica
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.forename: Isabel
authors.initials: I
authors.lastname: Barragan
authors.forename: Klaus
authors.initials: K
authors.lastname: Pors
authors.forename: Laurence
authors.initials: L
authors.lastname: Patterson
authors.forename: David
authors.initials: D
authors.lastname: Edler
authors.forename: Souren
authors.initials: S
authors.lastname: Mkrtchian
authors.forename: Inger
authors.initials: I
authors.lastname: Johansson
authors.forename: Magnus
authors.initials: M
authors.lastname: Ingelman-Sundberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072467:Cytochrome P450 Family 2; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012306:Risk
chemical_list: D003577:Cytochrome P-450 Enzyme System; C509336:CYP2W1 protein, human; D000072467:Cytochrome P450 Family 2